Atp6ap2 deletion causes extensive vacuolation that consumes the insulin content of pancreatic β cells

Significance Cells maintain several mechanisms to ensure their survival, including the removal of old or damaged proteins and organelles. This process must be balanced: too little turnover results in the accumulation of cellular “junk,” while excessive removal can deplete the cell and organism of key components. Here, we show that Atp6ap2 in the pancreatic β cell is essential for insulin granule turnover, as its absence resulted in the accumulation of oversized cytosolic vacuoles which conceivably account for excessive granule degradation, and thereby leads to impaired insulin secretion and diabetes.